Effects of cocaine-kindling on the expression of NMDA receptors and glutamate levels in mouse brain

Neurochem Res. 2011 Jan;36(1):146-52. doi: 10.1007/s11064-010-0284-2. Epub 2010 Oct 7.


In the present study we examined the effects of cocaine seizure kindling on the expression of NMDA receptors and levels of extracellular glutamate in mouse brain. Quantitative autoradiography did not reveal any changes in binding of [³H] MK-801 to NMDA receptors in several brain regions. Likewise, in situ hybridization and Western blotting revealed no alteration in expression of the NMDA receptor subunits, NR1 and NR2B. Basal overflow of glutamate in the ventral hippocampus determined by microdialysis in freely moving animals also did not differ between cocaine-kindled and control groups. Perfusion with the selective excitatory amino acid transporter inhibitor, pyrrolidine-2,4-dicarboxylic acid (tPDC, 0.6 mM), increased glutamate overflow confirming transport inhibition. Importantly, KCl-evoked glutamate overflow under tPDC perfusion was significantly higher in cocaine-kindled mice than in control mice. These data suggest that enhancement of depolarization stimulated glutamate release may be one of the mechanisms underlying the development of increased seizure susceptibility after cocaine kindling.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Brain* / drug effects
  • Brain* / metabolism
  • Brain* / physiopathology
  • Cocaine / pharmacology*
  • Dizocilpine Maleate / pharmacology
  • Dopamine Uptake Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism*
  • Kindling, Neurologic / drug effects*
  • Kindling, Neurologic / metabolism*
  • Male
  • Mice
  • Microdialysis
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*


  • Dopamine Uptake Inhibitors
  • Excitatory Amino Acid Antagonists
  • NR1 NMDA receptor
  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Dizocilpine Maleate
  • Cocaine